BRAF V600E confers male sex disease-specific mortality risk in patients with papillary thyroid cancer

PurposeTo test whether the prognostic risk of male sex in papillary thyroid cancer (PTC) is determined byBRAFV600E and can thus be stratified byBRAFstatus.Patients and MethodsWe retrospectively investigated the relationship between male sex and clinicopathologic outcomesin PTC, particularly mortality, with respect toBRAFstatus in 2,638 patients (male, n = 623; female, n =2,015) from 11 centers in six countries, with median age of 46 years (interquartile range, 35-58 years)at diagnosis and median follow-up time of 58 months (interquartile range, 26-107 months).ResultsDistant metastasis rates in men and women were not different in wild-typeBRAFPTC but weredifferent inBRAFV600E PTC: 8.9% (24 of 270) and 3.7% (30 of 817;P= .001), respectively. In wild-typeBRAFPTC, mortality rates were 1.4% (five of 349) versus 0.9% (11 of 1175) in men versuswomen (P= .384), with a hazard ratio (HR) of 1.59 (95% CI, 0.55 to 4.57), which remained in-significant at 0.70 (95% CI, 0.23 to 2.09) after clinicopathologic multivariable adjustment. InBRAFV600E PTC, mortality rates were 6.6% (18 of 272) versus 2.9% (24 of 822) in men versus women(P= .006), with an HR of 2.43 (95% CI, 1.30 to 4.53), which remained significant at 2.74 (95% CI,1.38 to 5.43) after multivariable adjustment. In conventional-variant PTC, male sex similarly had noeffect in wild-typeBRAFpatients; mortality rates inBRAFV600E patients were 7.2% (16 of 221)versus 2.9% (19 of 662) in men versus women (P= .004), with an HR of 2.86 (95% CI, 1.45 to 5.67),which remained significant at 3.51 (95% CI, 1.62 to 7.63) after multivariable adjustment.ConclusionMale sex is a robust independent risk factor for PTC-specific mortality inBRAFV600E patients butnot in wild-typeBRAFpatients. The prognostic risk of male sex in PTC can thus be stratified byBRAFstatus in clinical application